The regulation of dopamine transmission by metabotropic glutamate receptors

Receptor subtype nonselective metabotropic glutamate receptor (mGluR) agoni sts have been shown to regulate the release of dopamine. The eight mGluR su btypes have been pharmacologically categorized into three groups, and the p resent study used in vivo microdialysis to examine the capacity of mGluR su bgroup-selective drugs to modulate the extracellular levels of dopamine in the nucleus accumbens. By administering the drugs in the dialysis buffer, i t was found that the group 3 mGluR agonist L-amino-4-phosphonobutyrate prod uced a dose-dependent reduction in extracellular dopamine, whereas the grou p 1 agonist 3,5-dihydroxyphenylglycine was ineffective. The group 2 agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine produced a reduction that was biphasic with respect to dose. The group 2/3 antagonist alpha-meth yl-4-phosphnophenylglycine elicited a dose-dependent increase in extra; cel lular dopamine that was antagonized by coperfusion with either the L-type c alcium channel blocker diltiazem or the group 3 agonist L-amino-4-phosphono butyrate. These data demonstrate that group 3 and to a lesser extent group 2 mGluR may presynaptically regulate dopamine release or reuptake. Moreover , there exists significant in vivo glutamatergic tone on group 2/3 mGluRs t o suppress extracellular dopamine levels.